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dc.contributor.authorLo, JCY
dc.contributor.authorClark, AK
dc.contributor.authorAscui, N
dc.contributor.authorFrydenberg, M
dc.contributor.authorRisbridger, GP
dc.contributor.authorTaylor, RA
dc.contributor.authorWatt, MJ
dc.date.accessioned2020-12-22T05:35:06Z
dc.date.available2020-12-22T05:35:06Z
dc.date.issued2016-07-26
dc.identifierpii: 10258
dc.identifier.citationLo, J. C. Y., Clark, A. K., Ascui, N., Frydenberg, M., Risbridger, G. P., Taylor, R. A. & Watt, M. J. (2016). Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts. ONCOTARGET, 7 (30), pp.47650-47662. https://doi.org/10.18632/oncotarget.10258.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/258320
dc.description.abstractThere are established epidemiological links between obesity and the severity of prostate cancer. We directly tested this relationship by assessing tumorigenicity of patient-derived xenografts (PDXs) of moderate-grade localized prostate cancer in lean and obese severe combined immunodeficiency (SCID) mice. Mice were rendered obese and insulin resistant by high-fat feeding for 6 weeks prior to transplantation, and PDXs were assessed 10 weeks thereafter. Histological analysis of PDX grafts showed no differences in tumor pathology, prostate-specific antigen, androgen receptor and homeobox protein Nkx-3.1 expression, or proliferation index in lean versus obese mice. Whilst systemic obesity per se did not promote prostate tumorigenicity, we next asked whether the peri-prostatic adipose tissue (PPAT), which covers the prostate anteriorly, plays a role in prostate tumorigenesis. In vitro studies in a cellularized co-culture model of stromal and epithelial cells demonstrated that factors secreted from human PPAT are pro-tumorigenic. Accordingly, we recapitulated the prostate-PPAT spatial relationship by co-grafting human PPAT with prostate cancer in PDX grafts. PDX tissues were harvested 10 weeks after grafting, and histological analysis revealed no evidence of enhanced tumorigenesis with PPAT compared to prostate cancer grafts alone. Altogether, these data demonstrate that prostate cancer tumorigenicity is not accelerated in the setting of diet-induced obesity or in the presence of human PPAT, prompting the need for further work to define the at-risk populations of obesity-driven tumorigenesis and the biological factors linking obesity, adipose tissue and prostate cancer pathogenesis.
dc.languageEnglish
dc.publisherIMPACT JOURNALS LLC
dc.titleObesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.10258
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentPhysiology
melbourne.source.titleOncotarget
melbourne.source.volume7
melbourne.source.issue30
melbourne.source.pages47650-47662
dc.rights.licenseCC BY
melbourne.elementsid1191507
melbourne.contributor.authorRisbridger, Gail
melbourne.contributor.authorWatt, Matthew
dc.identifier.eissn1949-2553
melbourne.accessrightsOpen Access


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